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World Journal of Gastroenterology 2015年第1期21卷 60-83页

作者： nikolaos K Gatselis Kalliopi Zachou george K Koukoulis george n dalekos Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly41110 LarissaGreece Department of Pathology School of MedicineUniversity of Thessaly41110 LarissaGreece

Autoimmune hepatitis(AIH) is an unresolving progressive liver disease of unknown etiology characterized byhypergammaglobulinemia,autoantibodies detection and interface *** to the absence of specific diagnostic markers and the large heterogeneity of its clinical,laboratory and histological features,AIH diagnosis may be potentially ***,in this in-depth review we summarize the substantial progress on etiopathogenesis,clinical,serological and histological phenotypes of *** has a global distribution affecting any age,both sexes and all ethnic *** manifestations vary from asymptomatic to severe or rarely fulminant *** with selective elevation of IgG is found in most *** attack is perpetuated,possibly via molecular mimicry,and favored by the impaired control of T-regulatory ***(interface hepatitis,emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic,are still the hallmark for a timely *** remains a major diagnostic *** should be considered in every case in the absence of viral,metabolic,genetic and toxic etiology of chronic or acute *** personnel,hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient.

关键词： Autoimmune hepatitis Liver autoimmunity Liver-rela

Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece

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World Journal of Gastroenterology 2010年第2期16卷 225-231页

作者： Paraskevi Mina Sarah P Georgiadou Christos Rizos george n dalekos Eirini I Rigopoulou Department of Medicine and Research Laboratory of Internal Medicine Medical School University of Thessaly41110 LarissaThessalyGreece Research Group of Investigational Medicine Institute of Biomedical Research and TechnologyCentre for Research and Technology-Thessaly(CE.RE.TE.TH)41222 LarissaThessalyGreece RE.TE.TH)41222 LarissaThessalyGreece Research Group of Investigational Medicine Institute of Biomedical Research and TechnologyCentre for Research and Technology-Thessaly(CE.RE.TE.TH)41222 LarissaThessalyGreece

AIM:To assess the hepatitis B virus(HBV)-DnA and the prevalence of occult HBV infection in end-stage renal failure(ESRF)patients from Central Greece. METHODS:Sera from 366 ESRF patients attending five out of six dialysis units from Central Greece were investigated for HBV-DnA by real-time polymerase chain *** serum samples with repeatedly detectable HBV-DnA were considered *** antibodies to hepatitis C virus(anti-HCV)were tested by a third generation enzyme linked immunosorbent assay(ELISA),while IgG antibodies to hepatitis E virus (anti-HEV)were tested by two commercially available ***:HBV-DnA was detected in 15/366 patient (4.1%)and HBsAg in 20/366(5.5%).The prevalenc of occult HBV infection was 0.9%(3/346 HBsAg negative patients).Occult HBV was not associate with a specific marker of HBV infection or anti-HCV o anti-HEV *** was no significant differenc in HBV-DnA titres,demographic and biochemica features,between patients with occult HBV infectio and those with HBsAg-positive chronic HBV infection. COnCLUSIOn:In central Greece,4%of ESRF patient had detectable HBV-DnA,though in this setting,th prevalence of occult HBV seems to be very low(0.9%).

关键词： Hepatitis B virus-DnA Occult hepatitis B virus infection Haemodialysis Hepatitis B Real-time polymerase chain reaction

Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients

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World Journal of Gastroenterology 2012年第34期18卷 4721-4728页

作者： Theodoros A Zografos nikolaos Gatselis Kalliopi Zachou Christos Liaskos Stella Gabeta george K Koukoulis george n dalekos Depart ment of Medicine and Research Laboratory of Internal Medicine Medical SchoolUniversity of Thessaly41110 LarissaGreece Department of Pathology Medical SchoolUniversity of Thessaly41110 LarissaGreece

AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (AnA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific AnA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). COnCLUSIOn:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific AnA were not detected in anyone of PBC FDRs.

关键词： Primary biliary cirrhosis Antimitochondrial antibodies Anti-gp210 Anti-sp100 Liver autoimmunity

Individualization of chronic hepatitis C treatment according to the host characteristics

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World Journal of Gastroenterology 2014年第11期20卷 2839-2853页

作者： nikolaos K Gatselis Kalliopi Zachou Asterios Saitis Maria Samara george n dalekos Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly41110 LarissaGreece Department of Pathology School of MedicineUniversity of Thessaly41110 LarissaGreece

Hepatitis C virus(HCV)infection is a global health problem that affects more than 170 million people *** is a major cause of cirrhosis and hepatocellular carcinoma,making the virus the most common cause of liver failure and *** standardof-care treatment for chronic hepatitis C(CHC)has been changed during the last decade and direct acting antiviral drugs have already been ***,understanding of the pathogenesis of CHC has evolved rapidly during the last years and now several host factors are known to affect the natural history and response to *** genome-wide association studies have shown the important role of interleukin-28B and inosine triphosphatase in HCV *** present review article attempts to summarize the current knowledge on the role of host factors towards individualization of HCV treatment.

关键词： Chronic hepatitis C Hepatitis C virus host factors Interleukin 28B Inosine triphosphatase Single nucleotide polymorphism

Efficient management of secondary haemophagocytic lymphohistiocytosis with intravenous steroids and γ-immunoglobulin infusions

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World Journal of Clinical Cases 2019年第21期7卷 3394-3406页

作者： Sarah Georgiadou nikolaos K Gatselis Aggelos Stefos Kalliopi Zachou Konstantinos Makaritsis Eirini I Rigopoulou george n dalekos Department of Medicine and Research Laboratory of Internal Medicine University Hospital of LarissaLarissa 41110Greece Institute of Internal Medicine and Hepatology University Hospital of LarissaLarissa 41447Greece

BACKGROUnD Secondary haemophagocytic lymphohistiocytosis(sHLH)is a rare lifethreatening condition mainly associated with underlying infections,malignancies,and autoimmune or immune-mediated *** To analyse all sHLH cases that were diagnosed and managed under real-world circumstances in our department focusing on the treatment schedule and the *** Prospectively collected data from all adult patients fulfilling the criteria of sHLH who diagnosed and managed from January 1,2010 to June 1,2018,in our department of the tertiary care university hospital of Larissa,Greece,were analysed retrospectively(n=80;52%male;median age:55 years).The electronic records and/or written charts of the patients were reviewed for the demographic characteristics,clinical manifestations,underlying causes of sHLH,laboratory parameters,treatment schedule and 30-d-mortality *** of patients had received after consent intravenousγ-immunoglobulin(IVIG)for 5 d(total dose 2 g/kg)in combination with intravenous steroid pulses followed by gradual tapering of *** Seventy-five patients(94%)reported fever>38.5°C,47(59%)had liver or spleen enlargement and 76(95%)had ferritin>500 ng/mL including 20(25%)having considerably high levels(>10000 ng/mL).Anaemia and thrombocytopenia occurred in 72%and leucopoenia in 47%of *** infections were diagnosed in 59 patients(74%)as follows:leishmaniasis alone in 15/80(18.9%),leishmaniasis concurrently with Coxiella Burnetti or non-Hodgkin lymphoma in 2/80(2.5%),bacterial infections in 14/80(17.5%)including one case with concurrent non-Hodgkin lymphoma,viral infections in 13/80(16.3%),fungal infections in 2/80(2.5%),infections by mycobacteria in 1/80(1.3%)and unidentified pathogens in 12/80(15%).Seventy-two patients(90%)had received combination treatment with IVIG and intravenous ***,sHLH resolved in 76%of patients,15%died within the first month but 82.5%of patients were still alive 6 mo after ***

关键词： Haemophagocytic syndrome Haemophagocytic lymphohistiocytosis γ-immunoglobulin Leishmaniasis Ferritin

Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome

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World Journal of Hepatology 2013年第10期5卷 577-583页

作者： Eirini I Rigopoulou Kalliopi Zachou nikolaos K Gatselis Georgia Papadamou george K Koukoulis george n dalekos Department of Medicine and Research Laboratory of Internal Medicine Medical School University of Thessaly Department of Pathology Medical SchoolUniversity of Thessaly

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of ***: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P nitial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P nts with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during ***: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.

关键词： Antimitochindrial antibodies Autoimmune liver disease Hepatitis B virus Hepatitis C virus Primary biliary cirrhosis.

Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing cirrhosis and risk of hepatocellular carcinoma

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World Journal of Hepatology 2015年第14期7卷 1875-1883页

作者： Gary L norman nikolaos K Gatselis Zakera Shums Christos Liaskos Dimitrios P Bogdanos george K Koukoulis george n dalekos Inova Diagnostics Inc. Department of Medicine and Research Laboratory of Internal Medicine School of MedicineUniversity of Thessaly Division of Rheumatology School of MedicineUniversity of Thessaly Division of Transplantation Immunology and Mucosal Biology Institute of Liver StudiesKing’s College London School of MedicineDenmark Hill Campus Department of Pathology School of MedicineUniversity of Thessaly

AIM: To assess serum cartilage oligomeric matrix protein(COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma(HCC). METHODS: A COMP enzyme-linked immunosorbentassay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range(IQR)] duration of 96.5(102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study ***: COMP positivity(> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7%(14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age(P nced fibrosis(P = 0.001) and necroinflammatory activity(P = 0.001), higher aspartate aminotransferase(P nine aminotransferase(P nspeptidase(P = 0.003), alkaline phosphatase(P = 0.001), bilirubin(P nternational normalized ratio(P = 0.002) and alpha-fetoprotein levels(P nd lower albumin(P nd platelet count(P = 0.008). COMP levels [median(IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8(7.9) U

关键词： Hepatic fibrosis Hepatocellular carcinoma Viral hepatitis Enzyme-linked immunosorbent assay Biomarker Cirrhosis

Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients

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World Journal of Gastroenterology 2020年第34期26卷 5130-5145页

作者： nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L norman Mária Papp george n dalekos Department of Medicine and Research Laboratory of Internal Medicine National Expertise Center of Greece in Autoimmune Liver DiseasesGeneral University Hospital of LarissaLarissa 41110Greece Institute of Internal Medicine and Hepatology Larissa 41447Greece Department of Internal Medicine Division of GastroenterologyUniversity of DebrecenFaculty of MedicineDebrecen H-4032Hungary Department of Research and Development Inova DiagnosticsInc.San DiegoCA 92131United States

BACKGROUnD Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are *** this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial *** a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in ***,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in *** far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease *** To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease *** GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUAnTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all *** hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related *** duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted *** particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic *** Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of

关键词： Biomarker Golgi protein-73 Hepatic fibrosis Cirrhosis Hepatocellular carcinoma Hepatitis B Hepatitis C Aspartate aminotransferase/Platelets ratio index score

Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

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World Journal of Hepatology 2013年第7期5卷 387-392页

作者： Kalliopi Zachou Alexandros Sarantopoulos nikolaos K Gatselis Themistoklis Vassiliadis Stella Gabeta Aggelos Stefos Asterios Saitis Panagiota Boura george n dalekos Department of Medicine and Research Laboratory of Internal Medicine School of Medicine University of Thessaly Clinical Immunology Unit 2nd Department of Internal Medicine Hippokration General Hospital Aristotle University of Thessaloniki First Medical Propedeutic Department Medical School Aristotle University of Thessaloniki AHEPA Hospital Thessaloniki

AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DnA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. COnCLUSIOn: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

关键词： Immunosuppression Hepatitis B Antihepatitis B virus core antibody positivity Occult hepatitis B virus infection Rituximab

Symmetry transformations for magnetohydrodynamics and Chew–Goldberger–Low equilibria revisited

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Plasma Science and Technology 2019年第9期21卷 25-38页

作者： Achilleas EVAnGELIAS george n THROUMOULOPOULOS Department of Physics University of Ioannina section of Astrogeophysics

We generalize the symmetry transformations for magnetohydrodynamic(MHD) equilibria with isotropic pressure and incompressible flow parallel to the magnetic field introduced by Bogoyavlenskij in the case of the respective Chew–Goldberger–Low(CGL) equilibria with anisotropic pressure. We find that the geometrical symmetry of the field-aligned equilibria can be broken by those transformations only when the magnetic field is purely poloidal. In this situation we derive three-dimensional CGL equilibria from given axisymmetric ones. Also, we examine the generic symmetry transformations for MHD and CGL equilibria with incompressible flow of an arbitrary direction, introduced in a number of papers, and find that they cannot break the geometrical symmetries of the original equilibria, unless the velocity and magnetic field are collinear and purely poloidal.

关键词： symmetry transformations MHD equilibria breaking of geometrical symmetry plasma flow